Dose-Intense Cisplatin-Based Neoadjuvant Chemotherapy Increases Survival in Advanced Cervical Cancer: An Up-to-Date Meta-Analysis

SIMPLE SUMMARY: Although neoadjuvant chemotherapy has become standard care for many locally advanced cancer sites, the benefit of neoadjuvant chemotherapy remains unclear for the treatment of locally advanced cervical cancer. With this meta-analysis, we set out to demonstrate the benefit of using dose-intense cisplatin-based neoadjuvant chemotherapy in terms of overall survival and progression-free survival. Dose-intense cisplatin-based neoadjuvant chemotherapy followed by local therapy was significantly associated with a survival benefit in the treatment of locally advanced cervical carcinoma. Even though radiotherapy combined with weekly cisplatin-based chemotherapy remains standard of care for the treatment of locally advanced cervical cancer, our meta-analysis makes it possible to consider the use of dose-intense cisplatin-based neoadjuvant chemotherapy when local treatment is suboptimal and opens perspectives for designing new clinical trials in this setting. ABSTRACT: Purpose: We set out to demonstrate the benefit of using dose-intense cisplatin-based neoadjuvant chemotherapy in terms of overall survival and progression-free survival. Methods: We searched through MEDLINE and Cochrane Library databases up to May 2021 to identify randomized clinical trials comparing the benefit of using cisplatin-based neoadjuvant chemotherapy followed by local treatment with local treatment alone for the treatment of locally advanced cervical cancer. The PRISMA statement was applied. Results: Twenty-two randomized clinical trials were retrieved between 1991 and 2019, corresponding to 3632 women with FIGO stages IB2-IVA cervical cancer. More than 50% of the randomized clinical trials were assessed as having a low risk of bias. There was no benefit of neoadjuvant chemotherapy on overall survival, but there was significant heterogeneity across studies (I(2) = 45%, p = 0.01). In contrast, dose-intense cisplatin at over 72.5 mg/m(2)/3 weeks was significantly associated with increased overall survival (RR = 0.87, p < 0.05) with no heterogeneity across the pooled studies (I(2) = 36%, p = 0.11). The survival benefit was even greater when cisplatin was administered at a dose over 105 mg/m(2)/3 weeks (RR = 0.79, p < 0.05). Conclusion: Even though radiotherapy combined with weekly cisplatin-based chemotherapy remains standard of care for the treatment of locally advanced cervical cancer, our meta-analysis makes it possible to consider the use of dose-intense cisplatin-based neoadjuvant chemotherapy when local treatment is suboptimal and opens perspectives for designing new clinical trials in this setting. Neoadjuvant chemotherapy could be proposed when surgery is local treatment instead of standard chemoradiotherapy for the treatment of locally advanced cervical cancer.